Receptor theory predicts that fixed-proportion mixtures of a competitive, reversible agonist (e.g. fentanyl) and antagonist (e.g. naltrexone) at a common receptor (e.g. mu opioid receptors; MOR) will result in antagonist proportion-dependent decreases in apparent efficacy of the mixtures and downward shifts in mixture dose-effect functions. The present study tested this hypothesis by evaluating behavioral effects of fixed-proportion fentanyl/naltrexone mixtures in a warm-water tail-withdrawal procedure in rhesus monkeys (n=4)...

Although published literature provides a clear demonstration of widespread occurrence of opioid analgesics (OAs) in the aquatic environment, analytical methods suitable for a systematic study of this pharmaceutical class, which would include a broad spectrum of opioid analgesics and their metabolites, are still missing. In this work, a comprehensive multiresidue method for quantitative analysis of 27 opioid analgesics and their metabolites, including 2 morphine glucuronide conjugates, was developed and validated for three matrices: raw wastewater (RW), secondary effluent (SE) and river water...

Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer:solvent mixture at 37°C during 18h...

Pain management in end stage renal disease (ESRD) patients is a complex and challenging task to accomplish, and effective pain and symptom control improves quality of life. Pain is prevalent in more than 50% of hemodialysis patients and up to 75% of these patients are treated ineffectively due to its poor recognition by providers. A good history for PQRST factors and intensity assessment using visual analog scale are the initial steps in the management of pain followed by involvement of palliative care, patient and family counseling, discussion of treatment options, and correction of reversible causes...

INTRODUCTION: Vancouver, Canada is experiencing an opioid overdose crisis where fentanyl, a potent, synthetic opioid contaminating the illicit drug supply, has been detected in the majority of fatal overdose cases. Despite its growing presence throughout North America, few studies have characterized exposure to fentanyl among people who use illicit drugs (PWUD). We sought to identify the prevalence and correlates of fentanyl exposure among PWUD in Vancouver. METHODS: Data were derived from cohort studies of PWUD in Vancouver...

BACKGROUND AND PURPOSE: Opioids may inhibit the serotonin and norepinephrine transporters (SERT and NET, respectively). NET inhibition may contribute to analgesia, and SERT inhibition or interactions with serotonin receptors may cause serotonergic toxicity. However, the effects of different opioids on the human SERT, NET, and serotonin receptors have not been sufficiently studied. EXPERIMENTAL APPROACH: We determined the potencies of different opioids to inhibit the SERT and NET in vitro using human transporter-transfected cells...

BACKGROUND: Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone. AIM: The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions...

This report describes the outcomes of a process undertaken to review and update the National Safety Council's Alcohol, Drugs and Impairment Division's recommendations for the toxicological investigation of suspected alcohol and drug-impaired driving cases and motor vehicle fatalities. The updates to the recommendations are made based on a survey of practices in laboratories in the USA and Canada performing testing in these cases, consideration of existing epidemiological crash and arrest data, current drug use patterns, and practical considerations of widely available technology platforms in laboratories performing this work...

Macrophages (Mf) are a versatile group of phagocytic cells responsible for fulfilling a variety of immune functions, most notably for mounting the initial anti-microbial response and for the clearance of cellular debris and apoptotic bodies. The key processes for fulfilling these functions include the production of reactive oxygen intermediates (ROIs) and nitric oxide (NO). Mf also express a variety of receptors, including opioid, serotonin, and norepinephrine receptors, and thus can react to various substances...

BACKGROUND: Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'. OBJECTIVES: To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults...

PURPOSE: Although pharmaceutical claims are an essential data source for pharmacoepidemiological studies, these data potentially under-estimate opioid utilisation. Therefore, this study aimed to quantify the extent to which pharmaceutical claims from Australia's national medicines subsidy programs (Pharmaceutical Benefits Scheme [PBS] and Repatriation Schedule of Pharmaceutical Benefits [RPBS]) under-estimate prescription-only and total national opioid utilisation across time and for different opioids...

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action...

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia...

AIM OF THE STUDY: To compare analgesia and adverse effects during oral morphine and oxycodone and transdermal fentanyl and buprenorphine administration in cancer patients with pain. PATIENTS AND METHODS: Cancer patients treated at home and in outpatient clinics with severe pain (numerical rating scale score 6-10) fail to respond to non-opioids and/or weak opioids. All patients were randomized to either morphine, oxycodone, fentanyl or buprenorphine and divided into subgroups with predominant neuropathic and nociceptive pain component...

PURPOSE OF REVIEW: Chronic abdominal pain is a complex medical condition. The causes of chronic abdominal pain are extremely diverse ranging from chronic pancreatitis, Crohn's disease, to chronic pain with no clear etiology. Treatment of chronic abdominal pain remains a challenge in our clinical practice. While current interventions with celiac plexus blocks and pain medications provide some relief for these patients, but these treatments are typically less efficacious and limited by various adverse effects...

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents...

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences...